tbuckley/cabot-search huggingface dataset:
A large travel-associated outbreak of iatrogenic botulism in four European countries following intragastric botulinum neurotoxin injections for weight reduction, Türkiye, February to March 2023
Authors: Martin Bernhard Dorner, Hendrik Wilking, Martin Skiba, Laura Wilk, Maximilian Steinberg, Sylvia Worbs, Sabahat Çeken, Sedat Kaygusuz, Stéphanie Simon, François Becher, Agata Mikolajewska, Christian Kornschober, Timo Bütler, Nathalie Jourdan-Da-Silva, Maria an der Heiden, Lars Schaade, Klaus Stark, Brigitte Gertrud Dorner, Christina Frank
Journal: Eurosurveillance (2023)

In March 2023, 34 associated cases of iatrogenic botulism were detected in Germany (30 cases), Switzerland (two cases), Austria (one case), and France (one case). An alert was rapidly disseminated via European Union networks and communication platforms (Food- and Waterborne Diseases and Zoonoses Network, EpiPulse, Early Warning and Response System) and the International Health Regulation mechanism; the outbreak was investigated in a European collaboration. We traced sources of the botulism outbreak to treatment of weight loss in Türkiye, involving intragastric injections of botulinum neurotoxin. Cases were traced using a list of patients who had received this treatment. Laboratory investigations of the first 12 German cases confirmed nine cases. The application of innovative and highly sensitive endopeptidase assays was necessary to detect minute traces of botulinum neurotoxin in patient sera. The botulism notification requirement for physicians was essential to detect this outbreak in Germany. The surveillance case definition of botulism should be revisited and inclusion of cases of iatrogenic botulism should be considered as these cases might lack standard laboratory confirmation yet warrant public health action. Any potential risks associated with the use of botulinum neurotoxins in medical procedures need to be carefully balanced with the expected benefits of the procedure.
Risk factors for Hirschsprung disease-associated enterocolitis: a systematic review and meta-analysis
Authors: Xintao Zhang, Dong Sun, Qiongqian Xu, Han Liu, Yunfeng Li, Dongming Wang, Jian Wang, Qiangye Zhang, Peimin Hou, Weijing Mu, Chunling Jia, Aiwu Li
Journal: International Journal of Surgery (2023)

The incidence of Hirschsprung disease (HSCR) is nearly 1/5000 and patients with HSCR are usually treated through surgical intervention. Hirschsprung disease-associated enterocolitis (HAEC) is a complication of HSCR with the highest morbidity and mortality in patients. The evidence on the risk factors for HAEC remains inconclusive to date.Four English databases and four Chinese databases were searched for relevant studies published until May 2022. The search retrieved 53 relevant studies. The retrieved studies were scored on the Newcastle-Ottawa Scale by three researchers. Revman 5.4 software was employed for data synthesis and analysis. Stata 16 software was employed for sensitivity analysis and bias analysis.A total of 53 articles were retrieved from the database search, which included 10 012 cases of HSCR and 2310 cases of HAEC. The systematic analysis revealed anastomotic stenosis or fistula [ I2 =66%, risk ratio (RR)=1.90, 95% CI 1.34-2.68, P <0.001], preoperative enterocolitis ( I2 =55%, RR=2.07, 95% CI 1.71-2.51, P <0.001), preoperative malnutrition ( I2 =0%, RR=1.96, 95% CI 1.52-2.53, P <0.001), preoperative respiratory infection or pneumonia ( I2 =0%, RR=2.37, 95% CI 1.91-2.93, P <0.001), postoperative ileus ( I2 =17%, RR=2.41, 95% CI 2.02-2.87, P <0.001), length of ganglionless segment greater than 30 cm ( I2 =0%, RR=3.64, 95% CI 2.43-5.48, P <0.001), preoperative hypoproteinemia ( I2 =0%, RR=1.91, 95% CI 1.44-2.54, P <0.001), and Down syndrome ( I2 =29%, RR=1.65, 95% CI 1.32-2.07, P <0.001) as the risk factors for postoperative HAEC. Short-segment HSCR ( I2 =46%, RR=0.62, 95% CI 0.54-0.71, P <0.001) and transanal operation ( I2 =78%, RR=0.56, 95% CI 0.33-0.96, P =0.03) were revealed as the protective factors against postoperative HAEC. Preoperative malnutrition ( I2 =35 % , RR=5.33, 95% CI 2.68-10.60, P <0.001), preoperative hypoproteinemia ( I2 =20%, RR=4.17, 95% CI 1.91-9.12, P <0.001), preoperative enterocolitis ( I2 =45%, RR=3.51, 95% CI 2.54-4.84, P <0.001), and preoperative respiratory infection or pneumonia ( I2 =0%, RR=7.20, 95% CI 4.00-12.94, P <0.001) were revealed as the risk factors for recurrent HAEC, while short-segment HSCR ( I2 =0%, RR=0.40, 95% CI 0.21-0.76, P =0.005) was revealed as a protective factor against recurrent HAEC.The present review delineated the multiple risk factors for HAEC, which could assist in preventing the development of HAEC.
Liver transplantation for iatrogenic injuries secondary to cholecystectomy: a systematic review
Authors: Cristiano Guidetti, Ning Qi Pang, Barbara Catellani, Paolo Magistri, Daniela Caracciolo, Gian Piero Guerrini, Annarita Pecchi, Stefano Di Sandro, Fabrizio Di Benedetto
Journal: International Journal of Surgery (2023)

Introduction: Iatrogenic injury to the liver hilum during cholecystectomy is a severe surgical complication, with liver transplantation (LT) as the final drastic solution. We report the experience of our center and conduct a review of the literature on the outcomes of LT performed in this setting. Methods: Data sources included MEDLINE, EMBASE, and CENTRAL from inception to 19th June 2022. Studies reporting on patients treated with LT for liver hilar injuries following cholecystectomy were included. Incidence, clinical outcomes and survival data were synthesized through a narrative review. Results: 27 articles were identified, including 213 patients. 11(40.7%) articles highlighted deaths within 90-days post-LT. Post-LT mortality was reported in 28(13.1%) patients. Severe complications (≥Clavien III) occurred in at least 25.8%(n=55) of patients. Within larger cohorts, 1-year overall survival (OS) was 76.5–84.3%, and 5-year OS was 67.2–83.0%. We also highlight our own experience managing 14 patients with liver hilar injury secondary to cholecystectomy, of which two required LT. Conclusion: While short term morbidity and mortality is significant, available long-term data suggests reasonable OS in these patients following LT. Future studies are necessary to better understand the relationship between different types of liver hilar injury, transplant indication and outcomes of LT in this setting.
Projected Health Outcomes Associated With 3 US Supreme Court Decisions in 2022 on COVID-19 Workplace Protections, Handgun-Carry Restrictions, and Abortion Rights
Authors: Adam Gaffney, David U. Himmelstein, Samuel Dickman, Caitlin Myers, David Hemenway, Danny McCormick, Steffie Woolhandler
Journal: JAMA Network Open (2023)

Importance Several recent US Supreme Court rulings have drawn criticism from the medical community, but their health consequences have not been quantitatively evaluated. Objective To model health outcomes associated with 3 Supreme Court rulings in 2022 that invalidated workplace COVID-19 vaccine or mask-and-test requirements, voided state handgun-carry restrictions, and revoked the constitutional right to abortion. Design, Setting, and Participants This decision analytical modeling study estimated outcomes associated with 3 Supreme Court rulings in 2022: (1) National Federation of Independent Business v Department of Labor, Occupational Safety and Health Administration ( OSHA ), which invalidated COVID-19 workplace protections; (2) New York State Rifle and Pistol Association Inc v Bruen, Superintendent of New York State Police ( Bruen ), which voided state laws restricting handgun carry; and (3) Dobbs v Jackson Women’s Health Organization ( Dobbs ), which revoked the constitutional right to abortion. Data analysis was performed from July 1, 2022, to April 7, 2023. Main Outcomes and Measures For the OSHA ruling, multiple data sources were used to calculate deaths attributable to COVID-19 among unvaccinated workers from January 4 to May 28, 2022, and the share of these deaths that would have been prevented by the voided protections. To model the Bruen decision, published estimates of the consequences of right-to-carry laws were applied to 2020 firearm-related deaths (and injuries) in 7 affected jurisdictions. For the Dobbs ruling, the model assessed unwanted pregnancy continuations, resulting from the change in distance to the closest abortion facility, and then excess deaths (and peripartum complications) from forcing these unwanted pregnancies to term. Results The decision model projected that the OSHA decision was associated with 1402 additional COVID-19 deaths (and 22 830 hospitalizations) in early 2022. In addition, the model projected that 152 additional firearm-related deaths (and 377 nonfatal injuries) annually will result from the Bruen decision. Finally, the model projected that 30 440 fewer abortions will occur annually due to current abortion bans stemming from Dobbs , with 76 612 fewer abortions if states at high risk for such bans also were to ban the procedure; these bans will be associated with an estimated 6 to 15 additional pregnancy-related deaths each year, respectively, and hundreds of additional cases of peripartum morbidity. Conclusions and Relevance These findings suggest that outcomes from 3 Supreme Court decisions in 2022 could lead to substantial harms to public health, including nearly 3000 excess deaths (and possibly many more) over a decade.
Body-Plan Reorganization in a Sponge Correlates with Microbiome Change
Authors: Sergio Vargas, Laura Leiva, Michael Eitel, Franziska Curdt, Sven Rohde, Christopher Arnold, Michael Nickel, Peter Schupp, William D Orsi, Maja Adamska, Gert Wörheide
Journal: Molecular Biology and Evolution (2023)

Mounting evidence suggests that animals and their associated bacteria interact via intricate molecular mechanisms, and it is hypothesized that disturbances to the microbiome influence animal development. Here, we show that the loss of a key photosymbiont (i.e., bleaching) upon shading correlates with a stark body-plan reorganization in the common aquarium cyanosponge Lendenfeldia chondrodes. The morphological changes observed in shaded sponges include the development of a thread-like morphology that contrasts with the flattened, foliose morphology of control specimens. The microanatomy of shaded sponges markedly differed from that of control sponges, with shaded specimens lacking a well-developed cortex and choanosome. Also, the palisade of polyvacuolar gland-like cells typical in control specimens was absent in shaded sponges. The morphological changes observed in shaded specimens are coupled with broad transcriptomic changes and include the modulation of signaling pathways involved in animal morphogenesis and immune response, such as the Wnt, transforming growth factor β (TGF-β), and TLR-ILR pathways. This study provides a genetic, physiological, and morphological assessment of the effect of microbiome changes on sponge postembryonic development and homeostasis. The correlated response of the sponge host to the collapse of the population of symbiotic cyanobacteria provides evidence for a coupling between the sponge transcriptomic state and the state of its microbiome. This coupling suggests that the ability of animals to interact with their microbiomes and respond to microbiome perturbations has deep evolutionary origins in this group.
Application of metagenomic sequencing of drainage fluid in rapid and accurate diagnosis of postoperative intra-abdominal infection: a diagnostic study
Authors: Ruizhe Zhu, Xiafei Hong, Dong Zhang, Yi Xiao, Qiang Xu, Bin Wu, Junchao Guo, Xianlin Han, Qiwen Yang, Yupei Zhao, Wenming Wu
Journal: International Journal of Surgery (2023)

Postoperative intra-abdominal infection (PIAI) is one of the most serious complications of abdominal surgery, increasing the risk of postoperative morbidity and mortality and prolonging hospital stay. Rapid diagnosis of PIAI is of great clinical value. Unfortunately, the current diagnostic methods of PIAI are not fast and accurate enough.The authors performed an exploratory study to establish a rapid and accurate diagnostic method of PIAI. The authors explored the turnaround time and accuracy of metagenomic next-generation sequencing (mNGS) in diagnosing PIAI. Patients who underwent elective abdominal surgery and routine abdominal drainage with suspected PIAI were enroled in the study. The fresh midstream abdominal drainage fluid was collected for mNGS and culturing.The authors found that the median sample-to-answer turnaround time of mNGS was dramatically decreased than that of culture-based methods (<24 h vs. 59.5-111 h). The detection coverage of mNGS was much broader than culture-based methods. The authors found 26 species from 15 genera could only be detected by mNGS. The accuracy of mNGS was not inferior to culture-based methods in the 8 most common pathogens detected from abdominal drainage fluid (sensitivity ranged from 75 to 100%, specificity ranged from 83.3 to 100%, and kappa values were higher than 0.5). Moreover, the composition of the microbial spectrum established by mNGS varied between upper and lower gastrointestinal surgery, enhancing the understanding of PIAI pathogenesis.This study preliminarily revealed the clinical value of mNGS in the rapid diagnosis of PIAI and provided a rationale for further research.
The Genomic and Epigenomic Landscape of Double-Negative Metastatic Prostate Cancer
Authors: Arian Lundberg, Meng Zhang, Rahul Aggarwal, Haolong Li, Li Zhang, Adam Foye, Martin Sjöström, Jonathan Chou, Kevin Chang, Thaidy Moreno-Rodriguez, Raunak Shrestha, Avi Baskin, Xiaolin Zhu, Alana S. Weinstein, Noah Younger, Joshi J. Alumkal, Tomasz M. Beer, Kim N. Chi, Christopher P. Evans, Martin Gleave, Primo N. Lara, Rob E. Reiter, Matthew B. Rettig, Owen N. Witte, Alexander W. Wyatt, Felix Y. Feng, Eric J. Small, David A. Quigley
Journal: Cancer Research (2023)

Abstract Systemic targeted therapy in prostate cancer is primarily focused on ablating androgen signaling. Androgen deprivation therapy and second-generation androgen receptor (AR)–targeted therapy selectively favor the development of treatment-resistant subtypes of metastatic castration-resistant prostate cancer (mCRPC), defined by AR and neuroendocrine (NE) markers. Molecular drivers of double-negative (AR−/NE−) mCRPC are poorly defined. In this study, we comprehensively characterized treatment-emergent mCRPC by integrating matched RNA sequencing, whole-genome sequencing, and whole-genome bisulfite sequencing from 210 tumors. AR−/NE− tumors were clinically and molecularly distinct from other mCRPC subtypes, with the shortest survival, amplification of the chromatin remodeler CHD7, and PTEN loss. Methylation changes in CHD7 candidate enhancers were linked to elevated CHD7 expression in AR−/NE+ tumors. Genome-wide methylation analysis nominated Krüppel-like factor 5 (KLF5) as a driver of the AR−/NE− phenotype, and KLF5 activity was linked to RB1 loss. These observations reveal the aggressiveness of AR−/NE− mCRPC and could facilitate the identification of therapeutic targets in this highly aggressive disease. Significance: Comprehensive characterization of the five subtypes of metastatic castration-resistant prostate cancer identified transcription factors that drive each subtype and showed that the double-negative subtype has the worst prognosis.
Biomimetic Alveoli System with Vivid Mechanical Response and Cell–Cell Interface
Authors: Mengying Niu, Yujuan Zhu, Xiaoya Ding, Yan Zu, Yuanjin Zhao, Yongan Wang
Journal: Advanced Healthcare Materials (2023)

Alveolar microenvironmental models are important for studying the basic biology of the alveolus, therapeutic trials, and drug testing. However, a few systems can fully reproduce the in vivo alveolar microenvironment including dynamic stretching and the cell-cell interface. Here, a novel biomimetic alveolus-on-a-chip microsystem is presented suitable for visualizing physiological breathing for simulating the 3D architecture and function of human pulmonary alveoli. This biomimetic microsystem contains an inverse opal structured polyurethane membrane that achieves real-time observation of mechanical stretching. In this microsystem, the alveolar-capillary barrier is created by alveolar type 2 (ATII) cells cocultured with vascular endothelial cells (ECs) on this membrane. Based on this microsystem, the phenomena of flattening and the tendency of differentiation in ATII cells are observed. The synergistic effects of mechanical stretching and ECs on the proliferation of ATII cells are also observed during the repair process following lung injury. These features indicate the potential of this novel biomimetic microsystem for exploring the mechanisms of lung diseases, which can provide future guidance concerning drug targets for clinical therapies.
Sialic acid metabolism orchestrates transcellular connectivity and signaling in glioblastoma
Authors: Ugne Kuliesiute, Kevin Joseph, Jakob Straehle, Vidhya Madapusi Ravi, Jan Kueckelhaus, Jasim Kada Benotmane, Junyi Zhang, Andreas Vlachos, Juergen Beck, Oliver Schnell, Urte Neniskyte, Dieter Henrik Heiland
Journal: Neuro-Oncology (2023)

Abstract Background In glioblastoma (GBM), the effects of altered glycocalyx are largely unexplored. The terminal moiety of cell coating glycans, sialic acid, is of paramount importance for cell-cell contacts. However, sialic acid turnover in gliomas and its impact on tumor networks remain unknown. Methods We streamlined an experimental setup using organotypic human brain slice cultures as a framework for exploring brain glycobiology, including metabolic labeling of sialic acid moieties and quantification of glycocalyx changes. By live, 2-photon and high-resolution microscopy we have examined morphological and functional effects of altered sialic acid metabolism in GBM. By calcium imaging we investigated the effects of the altered glycocalyx on a functional level of GBM networks. Results The visualization and quantitative analysis of newly synthesized sialic acids revealed a high rate of de novo sialylation in GBM cells. Sialyltrasferases and sialidases were highly expressed in GBM, indicating that significant turnover of sialic acids is involved in GBM pathology. Inhibition of either sialic acid biosynthesis or desialylation affected the pattern of tumor growth and lead to the alterations in the connectivity of glioblastoma cells network. Conclusions Our results indicate that sialic acid is essential for the establishment of GBM tumor and its cellular network. They highlight the importance of sialic acid for glioblastoma pathology and suggest that dynamics of sialylation have the potential to be targeted therapeutically.
Public views are needed for skin colour scales
Authors: Stephanie J Lax, Amanda Roberts, Eleanor Cliffe, Grishma Ramesh, Dija Ayodele, Hywel C Williams, Sharon Belmo, Paul Leighton
Journal: British Journal of Dermatology (2023)

Our public engagement exercise showed that the Fitzpatrick Scale does not adequately represent how members of the public consider their own skin. Descriptions offered by respondents regarding their skin tone were richly varied; some also indicated that structured and embedded inequalities affected the language they used. The patient voice is key to developing comprehensive, inclusive and widely understood tools.
Leveraging preclinical study designs to close gaps in vaccine development for perinatal pathogens
Authors: Chelsea M. Crooks, Cliburn Chan, Sallie R. Permar
Journal: The Journal of Experimental Medicine (2023)

Vaccines to perinatal pathogens are critical for both reducing the burden of endemic pathogens and preparing for the next pandemic. Although they are often at greater risk of severe disease from infection, pregnant people and children are routinely marginalized in the vaccine development process. We highlight several challenges in the vaccine development process and how three tools—translational animal models, human cohort studies of natural infection, and innovative data-use strategies—can speed vaccine development and ensure equity for pregnant people and children in the next pandemic.
Alteration of the fecal microbiome in patients with cholecystectomy: potential relationship with postcholecystectomy diarrhea – before and after study
Authors: Choong-Kyun Noh, Woohyun Jung, Min Jae Yang, Wook Hwan Kim, Jae Chul Hwang
Journal: International Journal of Surgery (2023)

Bile acid (BA) is a crucial determinant of the gut microbiome, and cholecystectomy can alter the physiology of BA. Physiological changes in BA resulting from cholecystectomy can also influence the gut microbiome. We aimed to identify the specific taxa associated with perioperative symptoms, including postcholecystectomy diarrhea (PCD), and to evaluate the effect of cholecystectomy on the microbiome by investigating the fecal microbiome of patients with gallstones.We analyzed the fecal samples of 39 patients with gallstones (GS group) and 26 healthy controls (HC group) to evaluate their gut microbiome. We also collected fecal samples from GS group 3 months postcholecystectomy. Symptoms of patients were evaluated before and after cholecystectomy. Further, 16S ribosomal RNA amplification and sequencing were performed to determine the metagenomic profile of fecal samples.The microbiome composition of GS differed from that of HC; however, the alpha diversity was not different. No significant microbiome alterations were observed before and after cholecystectomy. Moreover, GS group showed a significantly lower Firmicutes to Bacteroidetes ratio before and after cholecystectomy than the HC group (6.2, P< 0.05). The inter-microbiome relationship was lower in GS than in HC and tended to recover 3 months after surgery. Furthermore, ~28.1% ( n =9) of patients developed PCD after surgery. The most prominent species among PCD (+) patients was Phocaeicola vulgatus. Compared with the preoperative state, Sutterellaceae , Phocaeicola , and Bacteroidals were the most dominant taxa among PCD (+) patients.GS group showed a different microbiome from that of HC; however, their microbiomes were not different 3 months after cholecystectomy. Our data revealed taxa-associated PCD, highlighting the possibility of symptom relief by restoring the gut microbiome.